tbuckley/cabot-search huggingface dataset:
Adherence to inhaled corticosteroids and long-acting β2-agonists in asthma: A MASK-air study
Authors: B. Sousa-Pinto, R. Louis, J.M. Anto, R. Amaral, A. Sá-Sousa, W. Czarlewski, L. Brussino, G.W. Canonica, C. Chaves Loureiro, A.A. Cruz, B. Gemicioglu, T. Haahtela, M. Kupczyk, V. Kvedariene, D.E. Larenas-Linnemann, Y. Okamoto, M. Ollert, O. Pfaar, N. Pham-Thi, F. Puggioni, F.S. Regateiro, J. Romantowski, J. Sastre, N. Scichilone, L. Taborda-Barata, M.T. Ventura, I. Agache, A. Bedbrook, S. Becker, K.C. Bergmann, S. Bosnic-Anticevich, M. Bonini, L.-P. Boulet, G. Brusselle, R. Buhl, L. Cecchi, D. Charpin, F. de Blay, S. Del Giacco, J.C. Ivancevich, M. Jutel, L. Klimek, H. Kraxner, P. Kuna, D. Laune, M. Makela, M. Morais-Almeida, R. Nadif, M. Niedoszytko, N.G. Papadopoulos, A. Papi, V. Patella, B. Pétré, D. Rivero Yeverino, C. Robalo Cordeiro, N. Roche, P.W. Rouadi, B. Samolinski, M. Savouré, M.H. Shamji, A. Sheikh, C. Suppli Ulrik, O.S. Usmani, A. Valiulis, A. Yorgancioglu, T. Zuberbier, J.A. Fonseca, E.M. Costa, J. Bousquet
Journal: Pulmonology (2023)

Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting β2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA.We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day.In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001).In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.
Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study
Authors: Linlin Zhang, Liuchun Wang, Jingya Wang, Jinliang Chen, Zhaoting Meng, Zhujun Liu, Xiangli Jiang, Xinyue Wang, Chun Huang, Peng Chen, Yan Liang, Richeng Jiang, Jing Wang, Diansheng Zhong, Yanhong Shang, Yan Zhang, Cuiying Zhang, Dingzhi Huang
Journal: Molecular Cancer (2023)

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and concurrent mutations have a poor prognosis. This study aimed to examine anlotinib plus icotinib as a first-line treatment option for advanced NSCLC carrying EGFR mutation with or without concurrent mutations.This phase 2, single-arm, multicenter trial (ClinicalTrials.gov NCT03736837) was performed at five hospitals in China from December 2018 to November 2020. Non-squamous NSCLC cases with EGFR-sensitizing mutations were treated with anlotinib and icotinib. The primary endpoint was progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity.Sixty participants were enrolled, including 31 (52%) and 29 (48%) with concurrent mutations and pathogenic concurrent mutations, respectively. The median follow-up was 26.9 (range, 15.0-38.9) months. ORR and DCR were 68.5% and 98.2%, respectively. Median PFS was 15.1 (95%CI: 12.6-17.6) months which met the primary endpoint, median DoR was 13.5 (95%CI: 10.0-17.1) months, and median OS was 30.0 (95%CI: 25.5-34.5) months. Median PFS and OS in patients with pathogenic concurrent mutations were 15.6 (95%CI: 12.5-18.7) months and not reached (95%CI: 17.46 months to not reached), respectively. All patients experienced TRAEs, including 26 (43%) and 1 (1.7%) who had grade ≥ 3 and serious treatment-related adverse events (TRAEs).Anlotinib combined with icotinib was effective and well-tolerated as a first-line treatment option for EGFR mutation-positive advanced NSCLC with or without concurrent mutations.ClinicalTrials.gov identifier: NCT03736837.
Sodium glucose co-transporter 2 inhibition increases epidermal growth factor expression and improves outcomes in patients with type 2 diabetes
Authors: Taha Sen, Wenjun Ju, Viji Nair, Patricia Ladd, Rajasree Menon, Edgar A. Otto, Laura Pyle, Tim Vigers, Robert G. Nelson, Clare Arnott, Bruce Neal, Michael K. Hansen, Matthias Kretzler, Petter Bjornstad, Hiddo J.L. Heerspink
Journal: Kidney International (2023)

Underlying molecular mechanisms of the kidney protective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors are not fully elucidated. Therefore, we studied the association between urinary epidermal growth factor (uEGF), a mitogenic factor involved in kidney repair, and kidney outcomes in patients with type 2 diabetes (T2D). The underlying molecular mechanisms of the SGLT2 inhibitor canagliflozin on EGF using single-cell RNA sequencing from kidney tissue were examined. Urinary EGF-to-creatinine ratio (uEGF/Cr) was measured in 3521 CANagliflozin cardioVascular Assessment Study (CANVAS) participants at baseline and week 52. Associations of uEGF/Cr with kidney outcome were assessed using multivariable-adjusted Cox regression models. Single-cell RNA sequencing was performed using protocol kidney biopsy tissue from ten young patients with T2D on SGLT2i, six patients with T2D on standard care only, and six healthy controls (HCs). In CANVAS, each doubling in baseline uEGF/Cr was associated with a 12% (95% confidence interval 1-22) decreased risk of kidney outcome. uEGF/Cr decreased after 52 weeks with placebo and remained stable with canagliflozin (between-group difference +7.3% (2.0-12.8). In young persons with T2D, EGF mRNA was primarily expressed in the thick ascending loop of Henle. Expression in biopsies from T2D without SGLT2i was significantly lower compared to HCs, whereas treatment with SGLT2i increased EGF levels closer to the healthy state. In young persons with T2D without SGLT2i, endothelin-1 emerged as a key regulator of the EGF co-expression network. SGLT2i treatment was associated with a shift towards normal EGF expression. Thus, decreased uEGF represents increased risk of kidney disease progression in patients with T2D. Canagliflozin increased kidney tissue expression of EGF and was associated with a downstream signaling cascade linked to tubular repair and reversal of tubular injury.
A Novel, Noninvasive Method to Diagnose Active Eosinophilic Esophagitis, Combining Clinical Data and Oral Cavity RNA Levels
Authors: Maialen Sebastian-Delacruz, Koldo Garcia-Etxebarria, Jose ramón Bilbao, Alfredo J. Lucendo, Luis Bujanda, Ainara Castellanos-Rubio
Journal: Clinical Gastroenterology and Hepatology (2023)

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and infiltration of eosinophils in the esophageal mucosa. According to the last published guideline for EoE diagnosis, obtaining at least 6 biopsies from a minimum of 2 esophageal locations is recommended, focusing on areas with endoscopic mucosal abnormalities. The cutoff of 15 eosinophils/per high-power field (HPF) is considered as the diagnostic threshold in a patient with symptoms of esophageal dysfunction.
Clinicogenomic Features and Targetable Mutations in NSCLCs Harboring BRAF Non-V600E Mutations: A Multi-Institutional Genomic Screening Study (LC-SCRUM-Asia)
Authors: Tetsuya Sakai, Shingo Matsumoto, Yasuto Ueda, Yuji Shibata, Takaya Ikeda, Atsushi Nakamura, Masahiro Kodani, Kadoaki Ohashi, Naoki Furuya, Hiroki Izumi, Kaname Nosaki, Shigeki Umemura, Yoshitaka Zenke, Hibiki Udagawa, Eri Sugiyama, Kiyotaka Yoh, Koichi Goto
Journal: Journal of Thoracic Oncology (2023)
Neonatal Cephalic Pustulosis
Authors: Wei-Cheng Fang, Li-Wen Chiu
Journal: New England Journal of Medicine (2023)

An 8-day-old boy was evaluated for a sudden-onset pustular rash. Erythematous papules and pustules were seen on the scalp, face, neck, and chest. A potassium hydroxide preparation showed fungal hyphae and spores.
Free the PrEP — Over-the-Counter Access to HIV Preexposure Prophylaxis
Authors: Douglas Krakower, Julia L. Marcus
Journal: New England Journal of Medicine (2023)

Interview with Douglas Krakower on the potential benefits associated with making preexposure prophylaxis for HIV available without a prescription. (19:02)Download Several barriers to access to preexposure prophylaxis for HIV could be alleviated by making it available over the counter. This step could particularly facilitate access among groups that face stigma.
Patient-reported Outcome Measurement and Reporting for Patients with Advanced Renal Cell Carcinoma: A Systematic Literature Review
Authors: Robert J. Motzer, Pratik P. Rane, Todd L. Saretsky, Deepshikha Pawar, Allison Martin Nguyen, Murali Sundaram, Joseph Burgents, Rishabh Pandey, Katja Rudell
Journal: European Urology (2023)
‘Evaluating the use of 18F-FDG PET/CT in the workup of Staphylococcus aureus bacteraemia: a cost-utility analysis’—Author's reply
Authors: Sean W.X. Ong, Alice Zhabokritsky, Nick Daneman, Steven Y.C. Tong, Harindra C. Wijeysundera
Journal: Clinical Microbiology and Infection (2023)
Segmentation in large-scale cellular electron microscopy with deep learning: A literature survey
Authors: Anusha Aswath, Ahmad Alsahaf, Ben N.G. Giepmans, George Azzopardi
Journal: Medical Image Analysis (2023)

Electron microscopy (EM) enables high-resolution imaging of tissues and cells based on 2D and 3D imaging techniques. Due to the laborious and time-consuming nature of manual segmentation of large-scale EM datasets, automated segmentation approaches are crucial. This review focuses on the progress of deep learning-based segmentation techniques in large-scale cellular EM throughout the last six years, during which significant progress has been made in both semantic and instance segmentation. A detailed account is given for the key datasets that contributed to the proliferation of deep learning in 2D and 3D EM segmentation. The review covers supervised, unsupervised, and self-supervised learning methods and examines how these algorithms were adapted to the task of segmenting cellular and sub-cellular structures in EM images. The special challenges posed by such images, like heterogeneity and spatial complexity, and the network architectures that overcame some of them are described. Moreover, an overview of the evaluation measures used to benchmark EM datasets in various segmentation tasks is provided. Finally, an outlook of current trends and future prospects of EM segmentation is given, especially with large-scale models and unlabeled images to learn generic features across EM datasets.
Financial Burden of Hepatocellular Carcinoma Screening in Patients With Cirrhosis
Authors: Manasa Narasimman, Ruben Hernaez, Vanessa Cerda, MinJae Lee, Sruthi Yekkaluri, Aisha Khan, Anubha Sood, Tami Gurley, Lisa Quirk, Yan Liu, Jennifer R. Kramer, Simon Craddock Lee, Jasmin A. Tiro, Caitlin C. Murphy, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2023)
Liquid‐Phase Integrated 3D Printed Biological Lenses for Lamellar Corneal Substitute
Authors: Qian Xue, Hanyi Hu, Weiwei Wang, Qi Li, Liang Ma, Jien Ma, Cathy Ye, Huayong Yang, Bin Zhang
Journal: Advanced Healthcare Materials (2023)

Abstract Compared to traditional biological lenses that are used to correct optical systems, such as contact lenses, vision correction surgery, and corneal and lens replacement, 3D printed biological lenses offer a customizable solutions. However, the layer‐by‐layer principle of 3D printing leads to a staircase effect, which cannot meet the critical requirements of surface quality during the manufacturing process of biological lens, particularly with soft materials. Here, a liquid‐phase printing strategy and a surface tension‐dependent (STD) post‐processing method are proposed that use the surface tension of the liquid to reconstruct the air‐liquid interface. This eliminates the staircase effect caused by the stacking of units during 3D printing. The coordinates of integrated printing enable high‐accuracy shape control of soft materials. Using a typical biological lens as an example, this method improves the surface quality of printed lamellar corneal substitutes (LCS) from ±20.0 to ±0.2 µm and reduces thickness feature size from ±500 to ±150 µm. This approach can match human cornea curvature and thickness, achieving ≈85% visible light transmittance and biocompatibility. Liquid‐phase 3D printed biological lenses outperform molded ones in animal experiments. This method can advance artificial biological lens printing research and holds promise for future clinical applications.
Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study
Authors: Yasushi Sano, Kinichi Hotta, Takahisa Matsuda, Yoshitaka Murakami, Takahiro Fujii, Shin-ei Kudo, Yasushi Oda, Hideki Ishikawa, Yutaka Saito, Nozomu Kobayashi, Masau Sekiguchi, Hiroaki Ikematsu, Atsushi Katagiri, Kazuo Konishi, Yoji Takeuchi, Hiroyasu Iishi, Masahiro Igarashi, Kiyonori Kobayashi, Miwa Sada, Shozo Osera, Tomoaki Shinohara, Yuichiro Yamaguchi, Kiwamu Hasuda, Toshitaka Morishima, Isao Miyashiro, Tadakazu Shimoda, Hirokazu Taniguchi, Takahiro Fujimori, Yoichi Ajioka, Shigeaki Yoshida
Journal: Clinical Gastroenterology and Hepatology (2023)
Impact of Clinical and Endoscopic Features on the Development of Metachronous Colorectal Advanced Serrated Lesions
Authors: Carol Rouphael, Jessica El Halabi, James Bena, John McMichael, Carol A. Burke
Journal: Clinical Gastroenterology and Hepatology (2023)

High-risk adenomas predict metachronous advanced adenomatous neoplasia. Limited data exist on predictors of metachronous advanced serrated lesions (mASLs). We analyzed clinical and endoscopic predictors of mASLs.
Rituximab administration in pediatric patients with newly diagnosed acute lymphoblastic leukemia
Authors: Keito Hoshitsuki, Yinmei Zhou, April M Miller, John K Choi, Hope D Swanson, Nickhill H Bhakta, Sima Jeha, Seth E Karol, Raul C Ribeiro, Jeffrey E Rubnitz, Charles G Mullighan, Cheng Cheng, Jun J Yang, Mary V Relling, Ching-Hon Pui, Hiroto Inaba
Journal: Leukemia (2023)
A novel germline PAX5 single exon deletion in a pediatric patient with precursor B-cell leukemia
Authors: N. van Engelen, M. Roest, F. van Dijk, E. Sonneveld, R. Bladergroen, S. V. van Reijmersdal, V. H. J. van der Velden, P. G. Hoogeveen, W. A. Kors, E. Waanders, M. C. J. Jongmans, R. P. Kuiper
Journal: Leukemia (2023)

Germline investigation in rare families with multiple affected individuals and large cohorts of pediatric patients with acute lymphoblastic leukemia (ALL) has resulted in the discovery of a growing number of leukemia predisposing genes [1, 2].A rare leukemia predisposition syndrome is caused by germline mutations in PAX5.Paired box 5 (PAX5) encodes for a paired box domain transcriptional factor essential for B-cell development [3].Approximately 30% of the pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor a somatic heterozygous loss-of-function alteration in PAX5 [4].Three germline missense variants in PAX5 have been described in seven families with a high incidence of BCP-ALL [5][6][7][8][9].The first germline PAX5 missense variant c.547G>A (p.Gly183Ser) was identified in four unrelated families [5,6,9].Functional testing showed that the PAX5 p.Gly183Ser variant has significantly reduced activity and results in deregulation of target genes, although the effect was milder than non-functional PAX5 mutants [5].A germline PAX5 missense variant affecting the same hotspot, c.547G>C (p.Gly183Arg), has been reported in one family [9].Two unrelated families were found to carry a germline c.113G>A (p.Arg38His) variant [7,8].Functional studies showed that PAX5 p.Arg38His is also a hypomorphic variant resulting in incomplete B-cell differentiation and is sufficient to predispose to leukemia [8].In all families, the susceptibility to BCP-ALL is inherited in an autosomal dominant pattern with incomplete penetrance.In the leukemia of the affected family members a second somatic alteration was detected in PAX5, either by loss of heterozygosity (LOH) or a second somatic mutation.We report a novel germline PAX5 alteration, a deletion including exon 6, in a boy who developed t(1;19)(q23;p13) (TCF3::PBX1) rearrangement-positive BCP-ALL at the age of 5. Somatic PAX5 aberrations are detected in ~20% of the cases with TCF3::PBX1 BCP-ALL [10].The patient was stratified in the standard risk group of the Dutch Childhood Oncology Group (DCOG) ALL11 treatment protocol and completed treatment without severe complications.He has been in follow up for three years.His father was diagnosed with acute undifferentiated leukemia at the age of 9 months.Cytogenetic testing of the leukemia of the father was not performed at time of diagnosis.
Emergence of high-level tigecycline resistance due to the amplification of a tet(A) gene variant in clinical carbapenem-resistant Klebsiella pneumoniae
Authors: Runhao Yu, Longyu Li, Chenhui Zou, Zheng Chen, Stefan Schwarz, Sheng Chen, Chunyan Xu, Hong Yao, Xiang-Dang Du
Journal: Clinical Microbiology and Infection (2023)
Genomic variants exclusively identified in children with birth defects and concurrent malignant tumors predispose to cancer development
Authors: Yichuan Liu, Hui-Qi Qu, Xiao Chang, Frank D Mentch, Haijun Qiu, Xiang Wang, Amir Hossein Saeidian, Deborah Watson, Joseph Glessner, Hakon Hakonarson
Journal: Molecular Cancer (2023)

Abstract Children with birth defects (BD) express distinct clinical features that often have various medical consequences, one of which is predisposition to the development of cancers. Identification of the underlying genetic mechanisms related to the development of cancer in BD patients would allow for preventive measures. We performed a whole genome sequencing (WGS) study on blood-derived DNA samples from 1566 individuals without chromosomal anomalies, including 454 BD probands with at least one type of malignant tumors, 767 cancer-free BD probands, and 345 healthy individuals. Exclusive recurrent variants were identified in BD-cancer and BD-only patients and mapped to their corresponding genomic regions. We observed statistically significant overlaps for protein-coding/ncRNA with exclusive variants in exons, introns, ncRNAs, and 3’UTR regions. Exclusive exonic variants, especially synonymous variants, tend to occur in prior exons locus in BD-cancer children. Intronic variants close to splicing site (&lt; 500 bp from exon) have little overlaps in BD-cancer and BD-only patients. Exonic variants in non-coding RNA (ncRNA) tend to occur in different ncRNAs exons regardless of the overlaps. Notably, genes with 5’ UTR variants are almost mutually exclusive between the two phenotypes. In conclusion, we conducted the first genomic study to explore the impact of recurrent variants exclusive to the two distinguished clinical phenotypes under study, BD with or without cancer, demonstrating enrichment of selective protein-coding/ncRNAs differentially expressed between these two phenotypes, suggesting that selective genetic factors may underlie the molecular processes of pediatric cancer development in BD children.
Collaborative strategies for deploying AI-based physician decision support systems: challenges and deployment approaches
Authors: Mirja Mittermaier, Marium Raza, Joseph C. Kvedar
Journal: npj Digital Medicine (2023)

AI-based prediction models demonstrate equal or surpassing performance compared to experienced physicians in various research settings. However, only a few have made it into clinical practice. Further, there is no standardized protocol for integrating AI-based physician support systems into the daily clinical routine to improve healthcare delivery. Generally, AI/physician collaboration strategies have not been extensively investigated. A recent study compared four potential strategies for AI model deployment and physician collaboration to investigate the performance of an AI model trained to identify signs of acute respiratory distress syndrome (ARDS) on chest X-ray images. Here we discuss strategies and challenges with AI/physician collaboration when AI-based decision support systems are implemented in the clinical routine.
Pump‐Less Platform Enables Long‐Term Recirculating Perfusion of 3D Printed Tubular Tissues
Authors: Feng Zhang, Dawn S. Y. Lin, Shravanthi Rajasekar, Alexander Sotra, Boyang Zhang
Journal: Advanced Healthcare Materials (2023)

Abstract The direction and pattern of fluid flow affect vascular structure and function, in which vessel‐lining endothelial cells exhibit variable cellular morphologies and vessel remodeling by mechanosensing. To recapitulate this microenvironment, some approaches have been reported to successfully apply unidirectional flow on endothelial cells in organ‐on‐a‐chip systems. However, these platforms encounter drawbacks such as the dependency on pumps or confinement to closed microfluidic channels. These constraints impede their synergy with advanced biofabrication techniques like 3D bioprinting, thereby curtailing the potential to introduce greater complexity into engineered tissues. Herein, a pumpless recirculating platform (UniPlate) that enables unidirectional media recirculation through 3D printed tubular tissues, is demonstrated.The device is made of polystyrene via injection molding in combination with 3D printed sacrifical gelatin templates. Tubular blood vessels with unidirectional perfusion are firstly engineered. Then the design is expanded to incorporate duo‐recirculating flow for culturing vascularized renal proximal tubules with glucose reabsorption function. In addition to media recirculation, human monocyte recirculation in engineered blood vessels is also demonstrated for over 24 h, with minimal loss of cells, cell viability, and inflammatory activation. UniPlate can be a valuable tool to more precisely control the cellular microenvironment of organ‐on‐a‐chip systems for drug discovery.
Comparison of 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT in Patients With SAPHO Syndrome
Authors: Peipei Wang, Chen Li, Guozhu Hou, Zhaohui Li, Hongli Jing, Wen Zhang, Fang Li
Journal: Clinical Nuclear Medicine (2023)

68Ga-DOTA-FAPI-04 PET/CT was performed on a cohort of 21 patients with known SAPHO syndrome. All patients underwent 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT on 2 consecutive days. The positive rates of the PET/CT scans at the sites of the osteoarticular symptom, the uptake values, and agreement with clinical osteoarticular symptom were compared.A total of 38 sites of involvement were detected. 18F-FDG PET/CT revealed 28 lesions. In contrast, 68Ga-DOTA-FAPI-04 PET/CT detected not only all lesions shown on 18F-FDG PET/CT but additional 10 lesions. 68Ga-DOTA-FAPI-04 scan also demonstrated significantly higher uptake and target-to-background ratio than 18F-FDG studies in the skeletal involvements. The agreement between 68Ga-DOTA-FAPI-04-positive lesions and current osteoarticular lesions was substantial (κ = 0.79, P < 0.001), whereas 18F-FDG had low to moderate agreement with clinical symptoms (κ = 0.52, P < 0.001).68Ga-DOTA-FAPI-04 has potential as a promising imaging agent for the evaluation of SAPHO syndrome.